Anita J Campbell1, Shakeel Mowlaboccus2, Geoffrey W Coombs3, Denise A Daley4, Laila S Al Yazidi5, Linny K Phuong6, Clare Leung7, Emma J Best8, Rachel H Webb9, Lesley Voss10, Eugene Athan11, Philip N Britton12, Penelope A Bryant13, Coen T Butters6, Jonathan R Carapetis14, Natasha S Ching15, Joshua Francis16, Te-Yu Hung17, Clare Nourse18, Samar Ojaimi19, Alex Tai20, Nan Vasilunas21, Brendan McMullan22, Asha C Bowen23, Christopher C Blyth24. 1. Department of Infectious Diseases, Perth Children's Hospital, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute. Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia. Electronic address: anita.campbell2@health.wa.gov.au. 2. College of Science, Health, Engineering and Education, Murdoch University, Murdoch; Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia; School of Biomedical Sciences, University of Western Australia, Nedlands. 3. College of Science, Health, Engineering and Education, Murdoch University, Murdoch; Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia. 4. Department of Microbiology, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Western Australia; The Australian Group on Antimicrobial Resistance (AGAR). 5. Child Health Department, Sultan Qaboos University Hospital, Muscat, Oman; Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, Australia; The Children's Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, NSW, Australia. 6. Department of General Medicine, Infectious Diseases Unit, Royal Children's Hospital, Melbourne, Australia; Infection and Immunity Group, Murdoch Children's Research Institute, Melbourne, Australia. 7. Department of Paediatrics, Wagga Wagga Base Hospital, New South Wales, Australia. 8. Department of Paediatrics; Child and Youth Health, The University of Auckland; The National Immunisation Advisory Centre, The University of Auckland; Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand. 9. Department of Paediatrics, Child and Youth Health, The University of Auckland; Department of Infectious Diseases Starship Children's Hospital, Auckland, New Zealand; Department of Paediatrics, Kidz First Hospital, Auckland, New Zealand. 10. Department of Paediatrics, Child and Youth Health, The University of Auckland; Department of Infectious Diseases, Starship Children's Hospital, Auckland, New Zealand. 11. Department of Infectious Disease, Barwon Health, Geelong, Australia; School of Medicine, Deakin University, Geelong, Australia. 12. Sydney Medical School and Marie Bashir Institute, University of Sydney, NSW, Australia; Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, Sydney, Australia. 13. Infectious Diseases Unit, Department of General Medicine, The Royal Children's Hospital, Parkville, Victoria, Australia; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia. 14. Department of Infectious Diseases, Perth Children's Hospital, Nedlands, Western Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia; University of Western Australia. School of Medicine, Perth, Western Australia. 15. Infection and Immunity, Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia; Department of General Paediatrics, Monash Children's Hospital, Monash Health, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Australia. 16. Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia; Department of Paediatrics, Royal Darwin Hospital, Darwin, Australia. 17. Department of Paediatrics, Royal Darwin Hospital, Darwin, Australia. 18. Queensland Children's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Australia. 19. Infection & Immunity, Monash Children's Hospital, Monash Health, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Australia; Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia. 20. Department of Infectious Disease, Barwon Health, Geelong, Australia. 21. Infectious Diseases Department, Women's and Children's Hospital, Adelaide. 22. Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, Australia; School of Women's and Children's Health, University of New South Wales, Sydney, Australia; National Centre for Infections in Cancer, University of Melbourne, Melbourne, Australia. 23. Department of Infectious Diseases, Perth Children's Hospital, Nedlands; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute; School of Medicine, University of Western Australia, Subiaco; Menzies School of Health Research, Charles Darwin Hospital, Darwin, NT. 24. Department of Infectious Diseases, Perth Children's Hospital, Nedlands; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute and School of Medicine, University of Western Australia; Department of Microbiology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia.
Abstract
OBJECTIVES: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. METHODS: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. RESULTS: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]). CONCLUSION: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.
OBJECTIVES: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. METHODS: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. RESULTS: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]). CONCLUSION: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.
Authors: Geoffrey W Coombs; Nicholas W T Yee; Denise Daley; Catherine M Bennett; James O Robinson; Marc Stegger; Princy Shoby; Shakeel Mowlaboccus Journal: Microorganisms Date: 2022-08-15